Randomized prospective trial of the effect of induced hypergastrinemia on the prevention of pancreatic atrophy after pancreatoduodenectomy in humans

Abstract

Objective: To investigate whether gastrin has regenerative effect on the pancreas and in particular whether it prevents the atrophy of the distal pancreas after resection of pancreas in humans.

Summary background data: Although pancreatic regeneration after resection is well documented in animals, atrophy rather than regeneration of the distal remnant pancreas commonly occurs following pancreatoduodenectomy in humans. Of the many factors involving pancreatic regeneration, gastrin has been shown to have trophic effect on the pancreas in an animal model.

Methods: Between March 1999 and May 2000, a randomized prospective study was performed in 56 patients who underwent pylorus-preserving pancreatoduodenectomy for periampullary neoplasms. Patients were allocated to either a lansoprazole group or a control group. The lansoprazole members were given oral lansoprazole (30 mg/d) over 12 weeks postoperatively to induce hypergastrinemia. During the study period, 19 patients were excluded for different reasons; in the end a total of 37 patients (lansoprazole, n = 18; control, n = 19) were eligible for study. The volume of the distal pancreas as determined using thin-sectioned spiral CT data, nutritional status, and endocrine (insulin level, glucose tolerance test) and exocrine function (stool elastase) of the pancreas and serum gastrin levels were measured before surgery and 3 months after surgery. The two groups were clinically comparable.

Results: Serum gastrin level was elevated in the lansoprazole group. In this group, the mean volume of the distal pancreas was reduced by 10% after pylorus-preserving pancreatoduodenectomy, whereas severe pancreatic atrophy occurred in the control group. Postoperative insulin and stool elastase levels were higher in the lansoprazole group than in the control group.

Conclusions: This study is the first prospective randomized trial of induced hypergastrinemia on the regeneration of the pancreas in humans. It may be possible to use induced hypergastrinemia in the treatment or prevention of pancreatic insufficiency following resection or injury.

Figure 1. Patient allocations.

Figure 2. Effect of lansoprazole (proton pump inhibitor) administration on serum gastrin level.

Figure 3. Individual volume changes of the distal pancreatic remnant in the lansoprazole group (A) and the control group (B).

Figure 4. Serum insulin levels in the lansoprazole group and the control group.

Figure 5. Stool elastase I levels in the lansoprazole group and the control group.